My wife is very tolerant of home theater gear, but she has always hated the 5+ remotes that seemed to float around the den. Never mind the, 'I want to listen to this CD, how do I do that?' questsions. Not that I'd ever tell anyone, but even I was tired of hunting through the 'remote basket' just to find the DVD player remote....
So I finally broke down and bought a Logitech Harmony 550 a couple of months ago. That's the 'cheap' one. I have tried the garden variety $40ish Wal-Mart universal remotes before, and have always hated them because they always just 'sort of' worked.
At first I didn't like the Harmony. It was certainly better than the cheaper ones I had used, but it didn't blow me away. Since the setup is all PC via USB based it was far easier than the usual code-punching of lesser remotes. But the default button setups were a mess and barely worked at doing anything other than turning stuff on, changing modes, and flipping channels. I understand that it would be impossible to automatically configure itself perfectly, so I dove deeper into the software.
After a couple of good solid hours of tinkering I finally had the remote working as expected. Then a few days later while tinkering a bit more I screwed up the remote's understanding of my receiver's inputs and could not figure out how to undo what I did. So I had to completely delete the receiver, which cascade-deleted all of the 'macros' and configurations that I had set up. Since the receiver is involved in everything, pretty much everything was affected. There's no backup & restore function in the software, so I had to start all over.
Now that it's all set up (again) and running the way I want, it's great. All of the main functions are grouped around an 'Activity'. Want to watch TV? Just press the 'Watch TV' button and the Harmony fires off all of the commands to power up & switch modes of devices. No explanations necessary, it's very easy. One power button shuts down the whole system. I have customized it to set sound modes, navigate to certain menus in my DishDVR, and so forth. It's very easy to use and my wife loves it.
It's a bit more tricky to use when it comes to 'custom' functions like changing modes on the SACD player or adjusting speaker level balances, but it works.
After using it for a couple of months and adjusting the remote and becomming used to how it works, I rarely touch any of my other remotes. My verdict? It takes some time and patience to set up, but once that's done it's great. I'm happy with it.
Oh, and FYI, the Logitech's will do 'other' devices too, such as lights and screens, so long as you have an IR (or RF, with a higher-end remote) interface to them.
He provides excellent service around here. If you are getting a HTM remote, I don't think you'll need to look any further than that! 
Like Jack, I have evolved to an MX-700 and MX-850. The 850 also has RF capability (get the more expensive RF component - more dependable).